Isolation and characterization of process related impurities and degradation products of bicalutamide and development of RP-HPLC method for impurity profile study

2008 ◽  
Vol 46 (3) ◽  
pp. 505-519 ◽  
Author(s):  
R. Nageswara Rao ◽  
A. Narasa Raju ◽  
R. Narsimha
Keyword(s):  
Degradation Products ◽  
Hplc Method ◽  
Impurity Profile ◽  
Related Impurities ◽  
Isolation And Characterization ◽  
Rp Hplc ◽  
Profile Study

IMPURITY PROFILING IMPURITY PROFILING OF THIAMINE HYDROCHLORIDE INJECTION BY RP-HPLC AND CHARACTERIZATION OF DEGRADATION PRODUCT BY LC-MS/MS/QTOF

2020 ◽  
pp. 151-161
Author(s):  
SRINIVASU KONDRA ◽  
BAPUJI A. T. ◽  
D. GOWRI SANKAR ◽  
POTTURI MURALI KRISHNAM RAJU
Keyword(s):  
Degradation Product ◽  
Degradation Products ◽  
Hplc Method ◽  
Thiamine Hydrochloride ◽  
Injectable Formulation ◽  
Hyphenated Technique ◽  
Isolation And Characterization ◽  
Impurity Profiling ◽  
Rp Hplc

Objective: To propose a comprehensive, simple, and affordable RP-HPLC method for impurity profiling and characterization of unknown degradation products of thiamine hydrochloride injectable formulation. Methods: The chromatographic separation employs gradient mode using the octadecyl silane column using a mobile phase consisting of phosphate buffer with ion pair reagent, acetonitrile, and methanol delivered flow rate at 1.2 ml/min. The detection was carried out at 248 nm using empower software. LC-MS/MS/QTOF hyphenated technique was used for isolation and characterization of unknown degradation impurity. The performance of the method was systematically validated as per ICH Q2 (R1) guidelines. Results: Degradation product observed in accelerated stability was characterized by LC-MS/MS/QTOF hyphenated technique and found m/z value 351.1604 and postulated as an oxidative degradation product of thiamine due to excipient interaction. The validated method was sensitive, selective, and specific data proves the method is precise and accurate from LOQ to 150% level and results are within 95-108% and less than 4.5% RSD. The developed method is linear from 0.03-58.83 µg/ml with a correlation coefficient of more than 0.990 and LOD and LOQ value ranged from 0.03 to1.51 μg/ml. Conclusion: An efficient RP-HPLC method for impurity profiling of thiamine injectable formulation was successfully developed and unknown degradation product observed instability condition samples characterized by LC-MS/MS/QTOF technique. The validated method can be successfully employed for the impurity profiling of thiamine injectable in the quality control department.

Identification, Characterization, and Quantification of Impurities of Safinamide Mesilate: Process-Related Impurities and Degradation Products

2017 ◽  
Vol 100 (4) ◽  
pp. 1029-1037 ◽  
Author(s):  
Liang Zou ◽  
Lili Sun ◽  
Hui Zhang ◽  
Wenkai Hui ◽  
Qiaogen Zou ◽  
...  
Keyword(s):  
Degradation Products ◽  
Hplc Method ◽  
Formation Mechanisms ◽  
Stability Indicating ◽  
Related Impurities ◽  
Related Substances ◽  
Water Ph ◽  
Bulk Drug ◽  
First Time

Abstract The characterization of process-related impurities and degradation products of safinamide mesilate (SAFM) in bulk drug and a stability-indicating HPLC method for the separation and quantification of all the impurities were investigated. Four process-related impurities (Imp-B, Imp-C, Imp-D, and Imp-E) were found in the SAFM bulk drug. Five degradation products (Imp-A, Imp-C, Imp-D, Imp-E, and Imp-F) were observed in SAFM under oxidative conditions. Imp-C, Imp-D, and Imp-E were also degradation products and process-related impurities. Remarkably, one new compound, identified as (S)-2-[4-(3-fluoro-benzyloxy) benzamido] propanamide (i.e., Imp-D), is being reported here as an impurity for the first time. Furthermore, the structures of the aforementioned impurities were characterized and confirmed via IR, NMR, and MS techniques, and the most probable formation mechanisms of all impurities proposed according to the synthesis route. Optimum separation was achieved on an Inertsil ODS-3 column (250 × 4.6 mm, 5 μm), using 0.1% formic acid in water (pH adjusted to 5.0) and acetonitrile as the mobile phase in gradient mode. The proposed method was found to be stability-indicating, precise, linear, accurate, sensitive, and robust for the quantitation of SAFM and its process-related substances, including its degradation products.

scholarly journals LC-MS characterization of acid degradation products of metoclopramide: Development and validation of a stability-indicating RP-HPLC method

2020 ◽  
Vol 11 (1) ◽  
pp. 781-789
Author(s):  
Sriram Valavala ◽  
Nareshvarma Seelam ◽  
Subbaiah Tondepu ◽  
Suresh Kandagatla
Keyword(s):  
Liquid Chromatography ◽  
Mobile Phase ◽  
Limit Of Detection ◽  
Degradation Products ◽  
Hplc Method ◽  
Limit Of Quantification ◽  
Stability Indicating ◽  
Rp Hplc ◽  
Hplc Technique

The present study aims to develop a simple, accurate and specific stability-indicating RP-HPLC technique for the analysis of metoclopramide in the presence of its stress degradation products and characterization of degradation compounds by LC-MS/MS analysis. As per ICH Q1A-R2 guidelines, the drug was exposed to acid hydrolytic stress condition. Three degradation products were formed for MCP in acid hydrolysis. The liquid chromatography was processed on a Luna C18-(2) 100A,250×4.6mm 5micron column using an isocratic mobile phase consisting of 0.1% formic acid in water-acetonitrile (20:80, v/v) by adjusting the mobile phase at 1 ml/min flow rate with wavelength detection at 273 nm. The developed procedure was applied to LC-MS/MS (liquid chromatography-tandem mass spectrometry) for the characterization of all the degradant components. Total new three degradation compounds were recognized and identified by LC-MS/MS. The developed RP-HPLC technique was validated as per the ICH Q2-R1 guidelines. Limit of detection and limit of quantification values of MCP were evaluated from the linearity graph and were found to be 5.23 µg/ml and 17.44 µg/ml. Accuracy study was established at 80.0, 100.0 and 120.0 µg/ml concentration levels and the findings were found in the range of 98.4% - 101.8%. The linearity of the technique was assessed over the drug concentration range of 50.0 µg/ml to 250.0 µg/ml and the regression equation, slope and correlation coefficient values were found to be y = 10618x + 1623.2, 10618 and 0.9996 respectively. The developed technique was uninterruptedly applied for the quantification of metoclopramide inactive pharmaceuticals.

Development and Validation of a Reversed-Phase High-Performance Liquid Chromatography (RP-HPLC) Method for Identification, Assay and Estimation of Related Substances of Ivermectin in Bulk Drug Batches of Ivermectin Drug Substance

2021 ◽  
Author(s):  
Daoli Zhao ◽  
Rasangi M Wimalasinghe ◽  
Lin Wang ◽  
Abu M Rustum
Keyword(s):  
High Performance Liquid Chromatography ◽  
Liquid Chromatography ◽  
High Performance ◽  
Degradation Products ◽  
Reversed Phase ◽  
Hplc Method ◽  
Drug Substance ◽  
Related Impurities ◽  
Rp Hplc ◽  
Bulk Drug

Abstract A reversed-phase high-performance liquid chromatography (RP-HPLC) method has been developed and validated for the identification and assay of Ivermectin, including the identification and estimation of its process-related impurities and degradation products in bulk drug substance of Ivermectin. Analytes were separated on a HALO C18 column (100 mm × 4.6 mm I.D., 2.7 μm particle size) maintained at 40 °C (column temperature) with gradient elution. All analytes of interests were adequately separated within 25 min. All degradation products, process-related impurities and assay were monitored by ultraviolet detection at 254 nm. The new HPLC method described here successfully separated an isomer peak of the active pharmaceutical ingredient (API) from the major API peak. This newly separated isomer peak is around 1.2 to 1.5% (peak area) in typical API samples, and coelutes with the major API peak by all current HPLC methods. Quantitation limit of the HPLC method is 0.1% of target analytical concentration (~1.0 μg/mL). This method has been demonstrated to be accurate, robust, significantly higher degree of selectivity compared to the HPLC methods of Ivermectin drug substance reported in the literature and in the compendial HPLC methods prescribed in the current USA and European Pharmacopeia.

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